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Photoporation with Biodegradable Polydopamine Nanosensitizers Enables Safe and Efficient Delivery of mRNA in Human T Cells
Author(s) -
Harizaj Aranit,
Wels Mike,
Raes Laurens,
Stremersch Stephan,
Goetgeluk Glenn,
Brans Toon,
Vandekerckhove Bart,
Sauvage Félix,
De Smedt Stefaan C.,
Lentacker Ine,
Braeckmans Kevin
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202102472
Subject(s) - photothermal therapy , electroporation , transfection , materials science , nanotechnology , context (archaeology) , cancer cell , cancer immunotherapy , nanoparticle , colloidal gold , biophysics , immunotherapy , cell culture , cancer , chemistry , biology , immune system , biochemistry , immunology , paleontology , genetics , gene
Abstract Safe and efficient production of chimeric antigen receptor (CAR)‐T cells is of crucial importance for cell‐based cancer immunotherapy. Physical transfection methods have quickly gained in importance in the context of transfecting T‐cells, since they are readily compatible with different cell types and a broad variety of cargo molecules. In particular, nanoparticle‐sensitized photoporation has been introduced in recent years as a gentle yet efficient method to transiently permeabilize cells, allowing subsequent entry of external cargo molecules into the cells. Gold nanoparticles (AuNPs) have been used the most as photothermal sensitizers because they can easily form laser‐induced vapor nanobubbles, a photothermal phenomenon that is shown to be particularly efficient for permeabilizing cells. However, as AuNPs are not biodegradable, clinical translation is hampered. Here, for the first time, the possibility to form laser‐induced vapor nanobubbles from biocompatible polymeric nanoparticles is reported. Compared to electroporation, the most used physical transfection method for T cells, 2.5 times more living mRNA transfected human T cells are obtained via photoporation sensitized by polydopamine nanoparticles. This shows that photoporation is a viable approach for efficiently producing therapeutic engineered T‐cells at a throughput easily exceeding 10 5 cells per second.